tbuckley/cabot-search huggingface dataset:
Complementary and Alternative Medicines in the Management of Heart Failure: A Scientific Statement From the American Heart Association
Authors: Sheryl L. Chow, Biykem Bozkurt, William L. Baker, Barry E. Bleske, Khadijah Breathett, Gregg C. Fonarow, Barry Greenberg, Prateeti Khazanie, Jacinthe Leclerc, Alanna A. Morris, Nosheen Reza, Clyde W. Yancy
Journal: Circulation (2022)

Complementary and alternative medicines (CAM) are commonly used across the world by diverse populations and ethnicities but remain largely unregulated. Although many CAM agents are purported to be efficacious and safe by the public, clinical evidence supporting the use of CAM in heart failure remains limited and controversial. Furthermore, health care professionals rarely inquire or document use of CAM as part of the medical record, and patients infrequently disclose their use without further prompting. The goal of this scientific statement is to summarize published efficacy and safety data for CAM and adjunctive interventional wellness approaches in heart failure. Furthermore, other important considerations such as adverse effects and drug interactions that could influence the safety of patients with heart failure are reviewed and discussed.
Zanubrutinib or Ibrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia
Authors: Jennifer R. Brown, Barbara Eichhorst, Peter Hillmen, Wojciech Jurczak, Maciej Kaźmierczak, Nicole Lamanna, Susan M. O’Brien, Constantine S. Tam, Lugui Qiu, Keshu Zhou, Martin Simkovic, Jiri Mayer, Amanda Gillespie-Twardy, Alessandra Ferrajoli, Peter S. Ganly, Robert Weinkove, Sebastian Grosicki, Andrzej Mital, Tadeusz Robak, Anders Osterborg, Habte A. Yimer, Tommi Salmi, Megan-Der-Yu Wang, Lina Fu, Jessica Li, Kenneth Wu, Aileen Cohen, Mazyar Shadman
Journal: New England Journal of Medicine (2022)

In a multinational, phase 3, head-to-head trial, ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, was compared with zanubrutinib, a BTK inhibitor with greater specificity, as treatment for relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). In prespecified interim analyses, zanubrutinib was superior to ibrutinib with respect to overall response (the primary end point). Data from the final analysis of progression-free survival are now available.
For-Profit Medical Schools — Concerns about Quality and Oversight
Authors: Robert Shireman
Journal: New England Journal of Medicine (2022)

Interview with Robert Shireman on policy changes allowing accreditation of for-profit medical schools in the United States. (08:16)Download The nonprofit-governance requirement for medical schools was a core component of U.S. medical care's transformation. But recently, several for-profit schools have been provisionally or fully accredited.
Loss of Y in leukocytes as a risk factor for critical COVID-19 in men
Authors: Bożena Bruhn-Olszewska, Hanna Davies, Daniil Sarkisyan, Ulana Juhas, Edyta Rychlicka-Buniowska, Magdalena Wójcik, Monika Horbacz, Marcin Jąkalski, Paweł Olszewski, Jakub O. Westholm, Agata Smialowska, Karol Wierzba, Åsa Torinsson Naluai, Niklas Jern, Lars-Magnus Andersson, Josef D. Järhult, Natalia Filipowicz, Eva Tiensuu Janson, Sten Rubertsson, Miklós Lipcsey, Magnus Gisslén, Michael Hultström, Robert Frithiof, Jan P. Dumanski
Journal: Genome Medicine (2022)

Abstract Background The COVID-19 pandemic, which has a prominent social and economic impact worldwide, shows a largely unexplained male bias for the severity and mortality of the disease. Loss of chromosome Y (LOY) is a risk factor candidate in COVID-19 due to its prior association with many chronic age-related diseases, and its impact on immune gene transcription. Methods Publicly available scRNA-seq data of PBMC samples derived from male patients critically ill with COVID-19 were reanalyzed, and LOY status was added to the annotated cells. We further studied LOY in whole blood for 211 COVID-19 patients treated at intensive care units (ICU) from the first and second waves of the pandemic. Of these, 139 patients were subject to cell sorting for LOY analysis in granulocytes, low-density neutrophils (LDNs), monocytes, and PBMCs. Results Reanalysis of available scRNA-seq data revealed LDNs and monocytes as the cell types most affected by LOY. Subsequently, DNA analysis indicated that 46%, 32%, and 29% of critically ill patients showed LOY above 5% cut-off in LDNs, granulocytes, and monocytes, respectively. Hence, the myeloid lineage that is crucial for the development of severe COVID-19 phenotype is affected by LOY. Moreover, LOY correlated with increasing WHO score (median difference 1.59%, 95% HDI 0.46% to 2.71%, p =0.025), death during ICU treatment (median difference 1.46%, 95% HDI 0.47% to 2.43%, p =0.0036), and history of vessel disease (median difference 2.16%, 95% HDI 0.74% to 3.7%, p =0.004), among other variables. In 16 recovered patients, sampled during ICU stay and 93–143 days later, LOY decreased significantly in whole blood and PBMCs. Furthermore, the number of LDNs at the recovery stage decreased dramatically (median difference 76.4 per 10,000 cell sorting events, 95% HDI 55.5 to 104, p =6e−11). Conclusions We present a link between LOY and an acute, life-threatening infectious disease. Furthermore, this study highlights LOY as the most prominent clonal mutation affecting the myeloid cell lineage during emergency myelopoiesis. The correlation between LOY level and COVID-19 severity might suggest that this mutation affects the functions of monocytes and neutrophils, which could have consequences for male innate immunity.
Incidence and burden of injury at the Tokyo 2020 Paralympic Games held during the COVID-19 pandemic: a prospective cohort study of 66 045 athlete days
Authors: Wayne Derman, Phoebe Runciman, Maaike Eken, Pieter-Henk Boer, Cheri Blauwet, Manos Bogdos, Guzel Idrisova, Esme Jordaan, James Kissick, Philipe LeVan, Jan Lexell, Fariba Mohammadi, Marcelo Patricio, Martin Schwellnus, Nick Webborn, Stuart E Willick, Kazuyoshi Yagishita
Journal: British Journal of Sports Medicine (2022)

Objective To describe the epidemiology of injuries at the Tokyo 2020 Paralympic Games, including injuries sustained in the new sports of badminton and taekwondo. Methods Injury data were obtained daily via the established web-based injury and illness surveillance system (WEB-IISS; 81 countries, 3836 athletes) and local organising committee medical facilities (81 countries, 567 athletes). Univariate unadjusted incidences (injuries per 1000 athlete days with 95% CIs), injury proportion (IP, %) and injury burden (days lost per 1000 athlete days) are reported. Results A total of 4403 athletes (1853 women, 2550 men) from 162 countries were monitored prospectively during the 3-day pre-competition and 12-day competition periods (66 045 athlete days). 386 injuries were reported in 352 athletes (IP=8.0%) with an incidence of 5.8 per 1000 athlete days (95% CI 5.3 to 6.5). Football 5-a-side (17.2), taekwondo (16.0), judo (11.6) and badminton (9.6) had the highest incidence. There was a higher incidence of injuries in the pre-competition period than in the competition period (7.5 vs 5.4; p=0.0053). Acute (sudden onset) injuries and injuries to the shoulder (0.7) and hand/fingers (0.6) were most common. Injury burden was 10.9 (8.6–13.8), with 35% of injuries resulting in time loss from training and competition. Conclusion Compared with previous Paralympic Games, there was a reduction in injury incidence but higher injury burden at the Tokyo 2020 Paralympic Games. The new sports of taekwondo and badminton had a high injury incidence, with the highest injury burden in taekwondo, compared with other sports. These findings provide epidemiological data to inform injury prevention measures for high-risk sports.
New sports, COVID-19 and the heat: sports injuries and illnesses in the Tokyo 2020 Summer Olympics
Authors: Torbjørn Soligard, Debbie Palmer, Kathrin Steffen, Alexandre Dias Lopes, Natalia Grek, Kentaro Onishi, Tomoyuki Shimakawa, Marie-Elaine Grant, Margo Mountjoy, Richard Budgett, Lars Engebretsen
Journal: British Journal of Sports Medicine (2022)

Objective To describe the incidence of injuries and illnesses sustained during the Tokyo Summer Olympic Games from 23 July to 8 August 2021. Methods We recorded the daily number of athlete injuries and illnesses (1) through the reporting of all National Olympic Committee (NOC) medical teams and (2) in the polyclinic and medical venues by the Tokyo 2020 medical staff. Results In total, 11 315 athletes (5423 women, 48%; 5892 men, 52%) from 206 NOCs were followed up prospectively for the occurrence of injury and illness. NOC and Tokyo 2020 medical staff reported 1035 injuries and 438 illnesses, equalling 9.1 injuries and 3.9 illnesses per 100 athletes over the 17-day period. Altogether, 9% of the athletes incurred at least one injury and 4% at least one illness. The incidence of injury was highest in boxing (27%), BMX racing (27%), BMX freestyle (22%), skateboarding (21%), karate (19%) and handball (18%), of which both BMX freestyle and skateboarding were new events, and lowest in diving, road cycling, rowing, marathon swimming and shooting (1–2%). Marathon and artistic swimming presented the highest illness incidences (both 8%), followed by skateboarding and karate (both 7%). In the study period, COVID-19 affected 18 athletes, accounting for 4% of all illnesses and 0.16% of all athletes. Exertional heat illness affected 78 athletes (18% of all illnesses, 0.7% of all athletes), the majority (88%) resulting in no time lost from sport. Conclusion Overall, 9% of the athletes incurred an injury and 4% an illness during the Games. Comprehensive countermeasures helped mitigate both COVID-19 and exertional heat illnesses.
Detection of chromosomal alteration after infusion of gene-edited allogeneic CAR T cells
Authors: Barbra J. Sasu, Gregory J. Opiteck, Suhasni Gopalakrishnan, Vivek Kaimal, Tom Furmanak, David Huang, Angshumala Goswami, Ying He, Jiamin Chen, Anh Nguyen, Arun Balakumaran, Nirav N. Shah, Mehdi Hamadani, Kathleen M. Bone, Sacha Prashad, Michael A. Bowen, Thomas Pertel, Heather D. Embree, Shalini G. Gidwani, David Chang, Alison Moore, Mark Leonard, Rafael G. Amado
Journal: Molecular Therapy (2022)

A chromosome 14 inversion was found in a patient who developed bone marrow aplasia following treatment with allogeneic chimeric antigen receptor (CAR) Tcells containing gene edits made with transcription activator-like effector nucleases (TALEN). TALEN editing sites were not involved at either breakpoint. Recombination signal sequences (RSSs) were found suggesting recombination-activating gene (RAG)-mediated activity. The inversion represented a dominant clone detected in the context of decreasing absolute CAR Tcell and overall lymphocyte counts. The inversion was not associated with clinical consequences and wasnot detected in the drug product administered to this patient or in any drug product used in this or other trials using the same manufacturing processes. Neither was the inversion detected in this patient at earlier time points or in any other patient enrolled in this or other trials treated with this or other product lots. This case illustrates that spontaneous, possibly RAG-mediated, recombination events unrelated to gene editing can occur in adoptive cell therapy studies, emphasizes the need for ruling out off-target gene editing sites, and illustrates that other processes, such as spontaneous V(D)J recombination, can lead to chromosomal alterations in infused cells independent of gene editing. A chromosome 14 inversion was found in a patient who developed bone marrow aplasia following treatment with allogeneic chimeric antigen receptor (CAR) Tcells containing gene edits made with transcription activator-like effector nucleases (TALEN). TALEN editing sites were not involved at either breakpoint. Recombination signal sequences (RSSs) were found suggesting recombination-activating gene (RAG)-mediated activity. The inversion represented a dominant clone detected in the context of decreasing absolute CAR Tcell and overall lymphocyte counts. The inversion was not associated with clinical consequences and wasnot detected in the drug product administered to this patient or in any drug product used in this or other trials using the same manufacturing processes. Neither was the inversion detected in this patient at earlier time points or in any other patient enrolled in this or other trials treated with this or other product lots. This case illustrates that spontaneous, possibly RAG-mediated, recombination events unrelated to gene editing can occur in adoptive cell therapy studies, emphasizes the need for ruling out off-target gene editing sites, and illustrates that other processes, such as spontaneous V(D)J recombination, can lead to chromosomal alterations in infused cells independent of gene editing.
Incidence and burden of illness at the Tokyo 2020 Paralympic Games held during the COVID-19 pandemic: a prospective cohort study of 66 045 athlete days
Authors: Wayne Derman, Phoebe Runciman, Maaike Eken, Pieter-Henk Boer, Cheri Blauwet, Manos Bogdos, Guzel Idrisova, Esme Jordaan, James Kissick, Philipe LeVan, Jan Lexell, Fariba Mohammadi, Marcelo Patricio, Martin Schwellnus, Nick Webborn, Stuart E Willick, Kazuyoshi Yagishita
Journal: British Journal of Sports Medicine (2022)

Objective To describe the incidence and burden of illness at the Tokyo 2020 Paralympic Games, which was organised with strict COVID-19 countermeasures. Methods Daily illnesses were recorded via the web-based injury and illness surveillance system (teams with their own medical staff; n=81), and local polyclinic services (teams without their own medical staff; n=81). Illness proportion, incidence and burden were reported for all illnesses and in subgroups by sex, age, competition period, sports and physiological system. Results 4403 athletes (1853 female and 2550 male) from 162 countries were monitored for the 15-day period of the Tokyo Paralympic Games (66 045 athlete days). The overall incidence of illnesses per 1000 athlete days was 4.2 (95% CI 3.8 to 4.8; 280 illnesses). The highest incidences were in wheelchair tennis (7.1), shooting (6.1) and the new sport of badminton (5.9). A higher incidence was observed in female compared with male athletes (5.1 vs 3.6; p=0.005), as well as during the precompetition versus competition period (7.0 vs 3.5; p&lt;0.0001). Dermatological and respiratory illnesses had the highest incidence (1.1 and 0.8, respectively). Illness burden was 4.9 days per 1000 athlete days and 23% of illnesses resulted in time loss from training/competition&gt;1 day. Conclusion The incidence of illness at the Tokyo 2020 Paralympic Games was the lowest yet to be recorded in either the summer or winter Paralympic Games. Dermatological and respiratory illnesses were the most common, with the burden of respiratory illness being the highest, largely due to time loss associated with COVID-19 cases. Infection countermeasures appeared successful in reducing respiratory and overall illness, suggesting implementation in future Paralympic Games may mitigate illness risk.
Endothelial METRNL determines circulating METRNL level and maintains endothelial function against atherosclerosis
Authors: Sili Zheng, Zhiyong Li, Jie Song, Pin Wang, Jian Xu, Wenjun Hu, Yi Shi, Qi Qi, Zhuwei Miao, Yunfeng Guan, Chaoyu Miao
Journal: Acta Pharmaceutica Sinica B (2022)

METRNL is a recently identified secreted protein with emerging functions. This study is to find major cellular source of circulating METRNL and to determine METRNL novel function. Here, we show METRNL is abundant in human and mouse vascular endothelium and released by endothelial cells using endoplasmic reticulum-Golgi apparatus pathway. By creating endothelial cell-specific Metrnl knockout mice, combined with bone marrow transplantation to produce bone marrow-specific deletion of Metrnl, we demonstrate that most of circulating METRNL (approximately 75%) originates from the endothelial cells. Both endothelial and circulating METRNL decrease in atherosclerosis mice and patients. By generating endothelial cell-specific Metrnl knockout in apolipoprotein E-deficient mice, combined with bone marrow-specific deletion of Metrnl in apolipoprotein E-deficient mice, we further demonstrate that endothelial METRNL deficiency accelerates atherosclerosis. Mechanically, endothelial METRNL deficiency causes vascular endothelial dysfunction including vasodilation impairment via reducing eNOS phosphorylation at Ser1177 and inflammation activation via enhancing NFκB pathway, which promotes the susceptibility of atherosclerosis. Exogenous METRNL rescues METRNL deficiency induced endothelial dysfunction. These findings reveal that METRNL is a new endothelial substance not only determining the circulating METRNL level but also regulating endothelial function for vascular health and disease. METRNL is a therapeutic target against endothelial dysfunction and atherosclerosis.
CircRNAs regulate the crosstalk between inflammation and tumorigenesis: The bilateral association and molecular mechanisms
Authors: Javeria Qadir, Shuo-yang Wen, Hui Yuan, Burton B. Yang
Journal: Molecular Therapy (2022)

Inflammation, a hallmark of cancer, has been associated with tumor progression, transition into malignant phenotype and efficacy of the chemotherapeutic agents in cancer. Chronic inflammation provides a favorable environment for tumorigenesis by inducing immunosuppression, whereas acute inflammation prompts tumor suppression by generating anti-tumor immune responses. Inflammatory factors derived from interstitial cells or tumor cells can stimulate cell proliferation and survival by modulating oncogenes and/or tumor suppressors. Recently, a new class of RNAs, i.e., circular RNAs (circRNAs), has been implicated in inflammatory diseases. Although there are reports on circRNAs imparting functions in inflammatory insults, whether these circularized transcripts hold the potential to regulate inflammation-induced cancer or tumor-related inflammation, and modulate the interactions between tumor microenvironment (TME) and the inflammatory stromal/immune cells, awaits further elucidation. Contextually, the current review describes the molecular association between inflammation and cancer, and spotlights the regulatory mechanisms by which circRNAs can moderate TME in response to inflammatory signals/triggers. We also present comprehensive information about the immune cell(s)-specific expression and functions of the circRNAs in TME, modulation of inflammatory signaling pathways to drive tumorigenesis, and their plausible roles in inflammasomes and tumor development. Moreover, the therapeutic potential of these circRNAs in harnessing inflammatory responses in cancer is also discussed.
Table of Contents
Authors: Roman Drozdowski, Natalie Spaccarelli, Margot Peters, Jane Grant-Kels, Dirk Elston, Brett Sloan, Jonathan Kantor, April Armstrong, Melinda Gooderham, Richard Warren, Kim Papp, Bruce Strober, Akimichi Morita, Jacek Szepietowski, Shinichi Imafuku, Elizabeth Colston, John Throup, Sudeep Kundu, Steve Schoenfeld, Misti Linaberry, Subhashis Banerjee, Andrew Blauvelt, Howard Sofen, Leon Kircik, Kenneth Gordon, Peter Foley, Phoebe Rich, Carle Paul, Jerry Bagel, Chitra Sekaran, Adrienne Shannon, Cimarron Sharon, Richard Straker, Michael Carr, Andrew Sinnamon, Kita Bogatch, Alexandra Ba, Nicholas Thaler, John Kelly, Graham Vetto, Danielle Fowler, Vernon Depalo, John Sondak, Mark Miura, Edmund Faries, Jonathan Bartlett, Giorgos Zager, Leonie Karakousis, Peter Schelke, Jonathan Kadouch, Arthur Swift, Lourdes Perez-Chada, Vanina Taliercio, Alice Gottlieb, Marta Van Beek, Kristina Duffin, Margo Reeder, Joseph Merola, Robert Swerlick, Krishan Parashar, Eloise Angeli, Wyatt Torres, Indermeet Boothby-Shoemaker, Jesse Kohli, Victor Neel, David Ozog, Loren Hernandez, Noreen Mohsin, Fabio Frech, Keyvan Nouri
Journal: Journal of the American Academy of Dermatology (2022)
Detection of Neonicotinoid Insecticides and Their Metabolites in Human Cerebrospinal Fluid
Authors: Adela Jing Li, Mengya Si, Renli Yin, Rongliang Qiu, Huashou Li, Fen Yao, Yunjiang Yu, Wenhua Liu, Zhen Wang, Xiaoyang Jiao
Journal: Environmental Health Perspectives (2022)
Longitudinal single-cell analysis of a patient receiving adoptive cell therapy reveals potential mechanisms of treatment failure
Authors: Rihao Qu, Yuval Kluger, Junchen Yang, Jun Zhao, David A. Hafler, Diane S. Krause, Alexey Bersenev, Marcus Bosenberg, Michael Hurwitz, Liliana Lucca, Harriet M. Kluger
Journal: Molecular Cancer (2022)

Abstract Adoptive cell therapy (ACT) using tumor infiltrating lymphocytes (TIL) is being studied in multiple tumor types. However, little is known about clonal cell expansion in vitro and persistence of the ACT product in vivo. We performed single-cell RNA and T-Cell Receptor (TCR) sequencing on serial blood and tumor samples from a patient undergoing ACT, who did not respond. We found that clonal expansion varied during preparation of the ACT product, and only one expanded clone was preserved in the ACT product. The TCR of the preserved clone which persisted and remained activated for five months was previously reported as specific for cytomegalovirus and had upregulation of granzyme family genes and genes associated with effector functions ( HLA-DQB1, LAT, HLA-DQA1, and KLRD1). Clones that contracted during TIL preparation had features of exhaustion and apoptosis . At disease progression, all previously detected clonotypes were detected. New clonotypes appearing in blood or tumor at disease progression were enriched for genes associated with cytotoxicity or stemness ( FGFBP2, GNLY, GZMH, GZMK, IL7R, SELL and KLF2 ), and these might be harnessed for alternative cellular therapy or cytokine therapy. In-depth single-cell analyses of serial samples from additional ACT-treated patients is warranted, and viral- versus tumor-specificity should be carefully analyzed.
RANKL-responsive epigenetic mechanism reprograms macrophages into bone-resorbing osteoclasts
Authors: Seyeon Bae, Kibyeong Kim, Keunsoo Kang, Haemin Kim, Minjoon Lee, Brian Oh, Kaichi Kaneko, Sungkook Ma, Jae Hoon Choi, Hojoong Kwak, Eun Young Lee, Sung Ho Park, Kyung-Hyun Park-Min
Journal: Cellular and Molecular Immunology (2022)
Clinical Characteristics and Outcomes of Patients Hospitalized With COVID-19 During the First 4 Waves in Zambia
Authors: Peter A. Minchella, Duncan Chanda, Jonas Z. Hines, Sombo Fwoloshi, Megumi Itoh, Davies Kampamba, Robert Chirwa, Suilanji Sivile, Khozya D. Zyambo, Simon Agolory, Lloyd B. Mulenga
Journal: JAMA Network Open (2022)

Few epidemiologic studies related to COVID-19 have emerged from countries in Africa, where demographic characteristics, epidemiology, and health system capacity differ from other parts of the world.